TY - JOUR
T1 - Efficacy of intravenous high-dose methotrexate in preventing relapse to the central nervous system in R-CHOP(-like)-treated, high-risk, diffuse large B-cell lymphoma patients and its effect on mortality
T2 - a systematic review and meta-analysis
AU - Tolley, Elisabeth R
AU - Lewinter, Christian
AU - Pedersen, Lars M
AU - Nielsen, Torsten Holm
PY - 2024/10/1
Y1 - 2024/10/1
N2 - Central nervous system (CNS) relapse in patients with diffuse large B-cell lymphoma (DLBCL) carries a dismal prognosis and most clinical guidelines recommend CNS prophylaxis to patients deemed at high risk of CNS relapse. However, results from observational studies investigating the effect of CNS prophylaxis have yielded conflicting results. The aims of this study were to evaluate: (i) whether addition of prophylactic intravenous high-dose methotrexate (HD-MTX) reduces the risk of CNS relapse in high-risk DLBCL patients treated with R-CHOP or similar, and (ii) whether HD-MTX prophylaxis confers an overall survival benefit, irrespective of CNS relapse. We performed a systematic search of MEDLINE/PubMed and EMBASE for data on DLBCL patients at high risk of CNS relapse treated with R-CHOP or similar who received HD-MTX as an intervention and a comparator arm of patients who did not receive prophylaxis and/or intrathecal prophylaxis. A risk of bias was estimated using the ROBINS-I tool and the quality of the evidence was assessed by the GRADE approach. Finally, a meta- analysis based on the systematic review was conducted. A total of 1,812 studies were screened. No randomized controlled trials were identified. Seven observational studies comprising 1,661 patients met the inclusion criteria. We found a statistically non-significant relative risk of 0.54 (95% confidence interval: 0.27-1.07) of CNS relapse for patients receiving HD-MTX versus controls. The meta-analysis investigating mortality demonstrated a relative risk of death of 0.70 (95% confidence interval: 0.44-1.11) for patients treated with HD-MTX versus controls. The overall risk of bias was adjudged as "serious" and the quality of the evidence was rated as "low". In conclusion, our data indicate that HD-MTX does not prevent or, at best, only slightly reduces the risk of CNS relapse and confers no survival benefit.
AB - Central nervous system (CNS) relapse in patients with diffuse large B-cell lymphoma (DLBCL) carries a dismal prognosis and most clinical guidelines recommend CNS prophylaxis to patients deemed at high risk of CNS relapse. However, results from observational studies investigating the effect of CNS prophylaxis have yielded conflicting results. The aims of this study were to evaluate: (i) whether addition of prophylactic intravenous high-dose methotrexate (HD-MTX) reduces the risk of CNS relapse in high-risk DLBCL patients treated with R-CHOP or similar, and (ii) whether HD-MTX prophylaxis confers an overall survival benefit, irrespective of CNS relapse. We performed a systematic search of MEDLINE/PubMed and EMBASE for data on DLBCL patients at high risk of CNS relapse treated with R-CHOP or similar who received HD-MTX as an intervention and a comparator arm of patients who did not receive prophylaxis and/or intrathecal prophylaxis. A risk of bias was estimated using the ROBINS-I tool and the quality of the evidence was assessed by the GRADE approach. Finally, a meta- analysis based on the systematic review was conducted. A total of 1,812 studies were screened. No randomized controlled trials were identified. Seven observational studies comprising 1,661 patients met the inclusion criteria. We found a statistically non-significant relative risk of 0.54 (95% confidence interval: 0.27-1.07) of CNS relapse for patients receiving HD-MTX versus controls. The meta-analysis investigating mortality demonstrated a relative risk of death of 0.70 (95% confidence interval: 0.44-1.11) for patients treated with HD-MTX versus controls. The overall risk of bias was adjudged as "serious" and the quality of the evidence was rated as "low". In conclusion, our data indicate that HD-MTX does not prevent or, at best, only slightly reduces the risk of CNS relapse and confers no survival benefit.
KW - Administration, Intravenous
KW - Antibodies, Monoclonal, Murine-Derived/administration & dosage
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - Central Nervous System Neoplasms/mortality
KW - Cyclophosphamide/administration & dosage
KW - Doxorubicin/administration & dosage
KW - Humans
KW - Lymphoma, Large B-Cell, Diffuse/mortality
KW - Methotrexate/administration & dosage
KW - Prednisone/administration & dosage
KW - Recurrence
KW - Rituximab/administration & dosage
KW - Treatment Outcome
KW - Vincristine/administration & dosage
UR - http://www.scopus.com/inward/record.url?scp=85205515752&partnerID=8YFLogxK
U2 - 10.3324/haematol.2023.284281
DO - 10.3324/haematol.2023.284281
M3 - Journal article
C2 - 38497149
SN - 0390-6078
VL - 109
SP - 3327
EP - 3337
JO - Haematologica
JF - Haematologica
IS - 10
ER -